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Biomedical subjects

Sanjaya Saxena

Publications and source records attributed to Sanjaya Saxena.

12 recordsLinked to original sources
PubMed2006

Paroxetine treatment of compulsive hoarding.

OBJECTIVE: Compulsive hoarding, found in many patients with obsessive-compulsive disorder (OCD), has been associated with poor response to serotonin reuptake inhibitor (SRI) medications in some reports. However, no prior study has quantitatively measured response to standardized pharmacotherapy in compulsive hoarders. We sought to determine whether compulsive hoarders would respond as well as non-hoarding OCD patients to the SRI, paroxetine. METHODS: Seventy-nine patients with OCD (32 patients with the compulsive hoarding syndrome and 47 patients without prominent hoarding symptoms) were treated openly with paroxetine (mean dose 41.6+/-12.8 mg/day; mean duration 80.4+/-23.5 days) according to a standardized protocol, from 3/1993 to 7/2005. All subjects were free of psychotropic medication for at least four weeks prior to study entry. No psychotherapy or psychotropic medications except paroxetine were allowed during the study period. Subjects were assessed before and after treatment with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Scale (Ham-A), Global Assessment Scale (GAS), and Clinical Global Impression/Improvement (CGI) scale. RESULTS: Both compulsive hoarders and non-hoarding OCD patients improved significantly with treatment (p<0.001), with nearly identical changes in Y-BOCS, HDRS, Ham-A, and GAS scores. There were no significant differences between groups in the proportions of patients who completed or responded to treatment. Hoarding symptoms improved as much as other OCD symptoms. CONCLUSIONS: Compulsive hoarders responded as well to paroxetine treatment as non-hoarding OCD patients, suggesting that SRI medications are effective for compulsive hoarding. Controlled trials of SRI medications for compulsive hoarding are now warranted.

Adult↗
PubMed2006

Gene variants of brain dopamine pathways and smoking-induced dopamine release in the ventral caudate/nucleus accumbens.

CONTEXT: Preclinical studies demonstrate that nicotine administration leads to dopamine release in the ventral striatum. However, human studies reveal considerable interindividual variability in the extent of smoking-induced dopamine release. OBJECTIVE: To determine whether common gene variants of the brain dopamine pathway explain this observed phenotypic variability in humans. DESIGN: Blood samples were drawn to determine gene variants of dopamine system components, and positron emission tomography scanning with the radiotracer raclopride labeled with radioactive carbon (11C) was performed to measure smoking-induced dopamine release. SETTING: Academic brain imaging center. PARTICIPANTS: Forty-five tobacco-dependent smokers. INTERVENTIONS: Subjects either smoked a cigarette (n = 35) or did not smoke (n = 10) during positron emission tomography scanning. MAIN OUTCOME MEASURES: Gene variants of dopamine system components (the dopamine transporter variable nucleotide tandem repeat, D2 receptor Taq A1/A2, D4 receptor variable nucleotide tandem repeat, and catechol-O-methyltransferase Val158Met polymorphisms) and change in [11C]raclopride binding potential in the ventral caudate/nucleus accumbens on positron emission tomography scans. RESULTS: For subjects who smoked during scanning, those with at least one 9 allele of the dopamine transporter variable nucleotide tandem repeat, fewer than 7 repeats of the D4 variable nucleotide tandem repeat, and the Val/Val catechol-O-methyltransferase genotype had greater decreases in binding potential (an indirect measure of dopamine release) with smoking than those with the alternate genotypes. An overall decrease in ventral caudate/nucleus accumbens binding potential in those who smoked compared with those who did not smoke was also found but was smaller in magnitude than previously reported. CONCLUSIONS: Smokers with genes associated with low resting dopamine tone have greater smoking-induced (phasic) dopamine release than those with alternate genotypes. These findings suggest that dopamine system genotype variabilities explain a significant proportion of the interindividual variability in smoking-induced dopamine release and indicate that smoking-induced dopamine release has a genetic predisposition.

Adult↗
PubMed2004

Attenuation of cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers: a preliminary study.

In untreated smokers, exposure to cigarette-related cues increases both the intensity of cigarette craving and relative glucose metabolism of the perigenual/ventral anterior cingulate cortex (ACC). Given that treatment with bupropion HCl reduces overall cigarette craving levels in nicotine dependent subjects, we performed a preliminary study of smokers to determine if bupropion HCl treatment attenuates cue-induced cigarette craving and associated brain metabolic activation. Thirty-seven, otherwise healthy smokers (20 untreated and 17 who had received open-label treatment with bupropion HCl) underwent two (18)F-fluorodeoxyglucose positron emission tomography scanning sessions in randomized order--one when presented with neutral cues and the other when presented with cigarette-related cues. Bupropion-treated smokers had smaller cigarette cue-induced increases in craving scores on the Urge to Smoke (UTS) Scale and less activation of perigenual/ventral ACC metabolism from the neutral to the cigarette cue scan than untreated smokers. Thus, in addition to its known effects on spontaneous cigarette craving and withdrawal symptoms, bupropion HCl diminishes cue-induced cigarette craving and appears to attenuate cigarette cue-induced ACC activation. These results are consistent with the known effects of bupropion HCl, including its enhancement of catecholaminergic neurotransmission.

Adult↗
PubMed2004

Treatment of compulsive hoarding.

Compulsive hoarding and saving symptoms, found in many patients who have obsessive-compulsive disorder (OCD), are part of a clinical syndrome that has been associated with poor response to antiobsessional medications and cognitive-behavioral therapy (CBT). Specific CBT strategies targeting the characteristic features of the compulsive hoarding syndrome have had better results. This article provides an overview of the compulsive hoarding syndrome, a review of treatment approaches and their efficacy, a case presentation, and a detailed discussion of intensive, multimodal CBT for compulsive hoarding. New insights into the neurobiological characteristics of compulsive hoarding that might direct future treatment development are also presented.

Antipsychotic Agents↗
PubMed2004

Cerebral glucose metabolism in obsessive-compulsive hoarding.

OBJECTIVE: Compulsive hoarding and saving symptoms, found in many patients with obsessive-compulsive disorder (OCD), are part of a discrete clinical syndrome that includes indecisiveness, disorganization, perfectionism, procrastination, and avoidance and has been associated with poor response to medications and cognitive behavior therapy. The authors sought to identify cerebral metabolic patterns specifically associated with the compulsive hoarding syndrome using positron emission tomography (PET). METHOD: [(18)F]Fluorodeoxyglucose PET scans were obtained for 45 adult subjects who met DSM-IV criteria for OCD (12 of whom had compulsive hoarding as their most prominent OCD symptom factor) and 17 normal comparison subjects. All subjects had been free of psychotropic medication for at least 4 weeks. Regional cerebral glucose metabolism was compared between the groups. RESULTS: In relation to the comparison subjects, the patients with compulsive hoarding syndrome had significantly lower glucose metabolism in the posterior cingulate gyrus and cuneus, whereas the nonhoarding OCD patients had significantly higher glucose metabolism in the bilateral thalamus and caudate. In relation to nonhoarding OCD patients, compulsive hoarders had significantly lower metabolism in the dorsal anterior cingulate gyrus. Across all OCD patients, hoarding severity was negatively correlated with glucose metabolism in the dorsal anterior cingulate gyrus. CONCLUSIONS: OCD patients with the compulsive hoarding syndrome had a different pattern of cerebral glucose metabolism than nonhoarding OCD patients and comparison subjects. Obsessive-compulsive hoarding may be a neurobiologically distinct subgroup or variant of OCD whose symptoms and poor response to anti-obsessional treatment are mediated by lower activity in the cingulate cortex.

Adult↗
PubMed2004

Augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder using adjunctive olanzapine: a placebo-controlled trial.

BACKGROUND: The purpose of this study was to explore the efficacy of adding an atypical antipsychotic, olanzapine, to a serotonin reuptake inhibitor (SRI) in treatment-refractory obsessive-compulsive disorder (OCD). METHOD: Twenty-six patients aged between 18 and 65 (mean = 41.2, SD = 11.9) years meeting DSM-IV criteria for OCD, who had not responded to SRIs, were treated for 6 weeks in a double-blind, placebo-controlled augmentation study with either olanzapine (up to 20 mg/day) or placebo. Severity of illness was assessed biweekly by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Analysis of covariance with baseline Y-BOCS score included as a covariate was used to compare improvement in Y-BOCS scores in the 2 groups. Response was defined as a 25% or greater improvement in Y-BOCS score. Data were collected between April 2001 and May 2003. RESULTS: Outcome was assessed for all patients using the last observation carried forward. Subjects in the olanzapine group had a mean decrease of 4.2 (SD = 7.9) in Y-BOCS score compared with a mean increase in score of 0.54 (SD = 1.31) for subjects in the placebo group (F = 4.85, df = 2,23; p =.04). Six (46%) of 13 subjects in the olanzapine group showed a 25% or greater improvement in Y-BOCS score compared with none in the placebo group. The final mean dose of olanzapine was 11.2 (SD = 6.5) mg/day. Medication was well tolerated. Only 2 (15%) of 13 subjects who received olanzapine discontinued because of side effects: sedation (N = 1) or weight gain (N = 1). CONCLUSION: These results provide preliminary evidence that adding olanzapine to SRIs is potentially efficacious and well tolerated in the short-term treatment of patients with refractory OCD. Controlled studies with larger sample sizes are necessary to more definitively address this treatment strategy.

Adult↗
PubMed2003

Differential brain metabolic predictors of response to paroxetine in obsessive-compulsive disorder versus major depression.

OBJECTIVE: Serotonin reuptake inhibitor (SRI) medications are effective in the treatment of both major depressive disorder and obsessive-compulsive disorder (OCD), but it is unknown whether the neural substrates of treatment response for the two disorders are the same or different. The authors sought to identify pretreatment cerebral glucose metabolic markers of responsiveness to SRI treatment in patients with OCD versus major depressive disorder and to determine whether the pretreatment patterns associated with improvement of OCD symptoms were the same as or different from those associated with improvement of major depressive disorder symptoms. METHOD: [(18)F]Fluorodeoxyglucose positron emission tomography was used to measure cerebral glucose metabolism in 27 patients with OCD alone, 27 with major depressive disorder alone, and 17 with concurrent OCD and major depressive disorder, who were all then treated with 30-60 mg/day of paroxetine for 8-12 weeks. Correlations were calculated between pretreatment regional metabolism and pre- to posttreatment changes in the severity of OCD symptoms, depressive symptoms, and overall functioning. RESULTS: While improvement of OCD symptoms was significantly correlated with higher pretreatment glucose metabolism in the right caudate nucleus (partial r=-0.53), improvement of major depressive disorder symptoms was significantly correlated with lower pretreatment metabolism in the amygdala (partial r=0.71) and thalamus (partial r=0.34) and with higher pretreatment metabolism in the medial prefrontal cortex and rostral anterior cingulate gyrus (Talairach coordinates: x=0, y=62, z=10) (z=2.91). CONCLUSIONS: These findings suggest that, although both OCD and major depressive disorder respond to SRIs, the two syndromes have different neurobiological substrates for response. Elevated activity in the right caudate may be a marker of responsiveness to antiobsessional treatment, while lower right amygdala activity and higher midline prefrontal activity may be required for response of depressive symptoms to treatment.

Adult↗
PubMed2002

Brain metabolic changes during cigarette craving.

BACKGROUND: In functional brain imaging studies, exposure to cues related to cocaine, opiates, and alcohol in dependent individuals is associated with activation of the anterior cingulate gyrus, amygdala, orbitofrontal cortex, and dorsolateral prefrontal cortex. Craving for these substances positively correlates with activity in the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior insula. The objective of this study was to determine changes in regional cerebral glucose metabolism and correlations between craving and regional metabolism in heavy cigarette smokers exposed to cigarette-related cues. METHODS: Twenty heavy smokers (who smoked > or =20 cigarettes per day) and 20 nonsmoking control subjects underwent 2 fluorine 18-fluorodeoxyglucose positron emission tomography scans 10 days apart in randomized order: one while watching a videotape that presented cigarette-related cues and handling a cigarette, and the other while watching an educational (nature) videotape and handling a neutral object (pen). RESULTS: From the neutral to the cigarette cue scan, heavy smokers had greater increases than nonsmoking controls in relative glucose metabolism in the perigenual anterior cingulate gyrus spanning the midline. Significant positive correlations were found between intensity of craving and metabolism in the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior insula bilaterally. An unexpected positive association was found between craving and metabolism in the right sensorimotor cortex. CONCLUSIONS: Brain regions associated with arousal, compulsive repetitive behaviors, sensory integration, and episodic memory are activated during exposure to cigarette-related cues and cigarette craving. These regional brain activations and associations with craving are similar to findings with other addictive substances.

Adult↗
PubMed2002

Differential cerebral metabolic changes with paroxetine treatment of obsessive-compulsive disorder vs major depression.

BACKGROUND: Serotonin reuptake inhibitors (SRIs) effectively treat both major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). We compared and contrasted the functional neuroanatomical effects of SRIs in OCD and MDD as these 2 disorders occurred separately and concurrently by measuring pretreatment to posttreatment cerebral glucose metabolic changes in OCD vs MDD vs concurrent OCD + MDD. METHODS: We obtained [(18)F]fluorodeoxyglucose positron emission tomography (PET) brain scans on 25 subjects with OCD, 25 with MDD, and 16 with concurrent OCD + MDD before and after 8 to 12 weeks of treatment with paroxetine hydrochloride. Controls (n = 16) were scanned 10 to 12 weeks apart without treatment. Treatment response was defined as a more than 25% decline in OCD symptom severity, a more than 50% decline in MDD severity, and "much improved" clinical global impression. RESULTS: Although all patient groups received the same paroxetine dose for the same duration, regional metabolic changes differed significantly among diagnostic groups. Subjects with OCD alone showed significant metabolic decreases in the right caudate nucleus, right ventrolateral prefrontal cortex (VLPFC), bilateral orbitofrontal cortex, and thalamus that were not seen in any other group. Both the MDD and concurrent OCD + MDD groups showed metabolic decreases in the left VLPFC and increases in the right striatum. Treatment response was associated with a decrease in striatal metabolism in nondepressed OCD patients but with an increase in striatal activity in patients with OCD + MDD. CONCLUSIONS: Brain metabolic responses to SRIs are both disorder-specific and response-specific. They vary according to the underlying pathophysiology of the patient and the degree of symptomatic improvement.

Adult↗
PubMed2002

Obsessive-compulsive hoarding: symptom severity and response to multimodal treatment.

BACKGROUND: Compulsive hoarding and saving symptoms, found in many patients with obsessive-compulsive disorder (OCD), are part of a clinical syndrome that has been associated with poor response to medications and cognitive-behavioral therapy (CBT). We sought to determine whether patients with the compulsive hoarding syndrome had more severe symptoms and functional impairment than nonhoarding OCD patients and whether they would respond to intensive, multimodal treatment previously found to be effective for treatment-refractory OCD. METHOD: We studied 190 consecutive patients with DSM-IV OCD treated openly for approximately 6 weeks with intensive CBT, medication, and psychosocial rehabilitation in a partial hospitalization program for severely ill OCD patients. Twenty of the 190 patients (11%) were identified as having the compulsive hoarding syndrome. All patients were assessed before and after treatment with the Yale-Brown Obsessive Compulsive Scale (YBOCS), Hamilton Rating Scale for Depression (HAM-D). Hamilton Rating Scale for Anxiety (HAM-A). and Global Assessment Scale (GAS). We compared the symptom severity and response to treatment of compulsive hoarders versus nonhoarding OCD patients. RESULTS: Compulsive hoarders were significantly older than nonhoarders (p < .001). Hoarders had significantly lower GAS scores and higher HAM-A scores than nonhoarders both before (p = .04) and after (p = .002) treatment, but had similar pretreatment YBOCS scores. Both groups improved significantly with treatment as assessed by YBOCS score (p < .001), but nonhoarders had significantly greater decreases in YBOCS scores than hoarders (p = .02). CONCLUSION: While the compulsive hoarding syndrome appears to be a distinct, more disabling, variant of OCD that does not respond as robustly to treatment, it may still improve significantly with intensive, multimodal treatment tailored to its specific features and associated deficits.

Adolescent↗
PubMed2002

Refractory obsessive-compulsive disorder: state-of-the-art treatment.

Nonresponse to treatment in obsessive-compulsive disorder is common, associated with substantial impairment, and understudied. Little practical advice is available to clinicians on next-step treatment strategies for patients who have not responded well to 2 trials of selective serotonin reuptake inhibitors (SSRIs). Available options include continuation of SSRI treatment, switching to another SSRI or selective serotonin-norepinephrine reuptake inhibitor, augmenting with atypical neuroleptics or cognitive-behavioral therapy, or utilizing novel treatment approaches. The authors synthesize state-of-the-art treatment and give practical advice for clinicians.

Antipsychotic Agents↗